About TIE1, TIE2 / Angiopoietin:
Both TIE 1 and TIE 2 receptors are part of the family of receptor tyrosine kinases. Alongside angiopoietins and the ligands of the TIE 2 receptor, they are essential for the formation of new blood vessels.
TIE1, TIE2 Function
TIE 1 and TIE 2 receptors form part of the cellular signaling pathway for endothelial cells that line the vascular system throughout the body. Research has shown that receptors in this class are vital for healthy endothelial function. Mice grown without these receptors quickly see malformation of their blood vessels and die within just a few days.
The belief is that the receptors play an important role in the formation of blood vessels inside the developing embryo. Mice embryos that are deficient in TIE receptors go on to develop malformations, both in the heart and the rest of the cardiovascular structure, making them unviable.
Why precisely there are malformations is not yet entirely understood. Stretching of the cells of the endothelium in subsequent experiments, however, reveal that they are not as flexible in mice with TIE receptor deficiency, suggesting that the receptors play an essential role in cardiovascular dilation. The tissue could not contract correctly, and some vascular segments collapsed, preventing the passage of blood through the body of the mouse.
The nature of the malformation of blood vessels suggested that the affected mice would not have been able to perform gas exchange. The finding that there were lots of dead cells throughout the embryonic material adds support to this argument.
Angiopoietin Receptor Mechanism
TIE receptors perform a role in assuring the correct structure of cardiovascular tissues in angiogenesis, but they are not the only factor involved in blood vessel formation. Research suggests that angiopoietin-1 also plays a vital role.
The data so far support the notion that TIE 1 and angiopoietin together support a process known as endothelial spouting but not endothelial proliferation or tube formation in vitro. More evidence suggests that angiopoietin is only weakly mitogenic, implying that further factors are involved in the creation of blood vessels in developing animals.
TIE1, TIE2 Structure
TIE 1 receptor tyrosine kinase was initially believed to have a stabilizing effect on blood vessels and the blood vessel walls. Mice without the TIE 1 receptor exhibited holes in their blood vessel walls and necrotic tissues.
Recently, a more detailed picture has begun to emerge of the effects of eliminating the TIE 1 receptor. Samples from mice with TIE 1 knocked out show that the blood vessels were both malformed but also extremely dense. The lack of TIE 1 receptor put them into hypergrowth mode, creating a far denser network than would generally be expected. Blood vessels also connected to themselves in ways that they wouldn’t ordinarily. For instance, cellular filopodia projected into the vessel lumen and attached to the opposite wall.
Thus, the evidence appears to suggest that TIE 1 is a modulator of angiogenesis, inhibiting the overgrowth that can occur without its presence.
Mice with both TIE 1 and TIE 2 knocked out exhibit similar mutant characteristics to TIE 2 knockout mice, but with earlier-onset symptoms.